American Journal of Cardiovascular Drugs

, Volume 12, Issue 4, pp 255–262 | Cite as

Comparison of Hyperkalemic Risk in Hospitalized Patients Treated with Different Angiotensin Receptor Blockers

A Retrospective Cohort Study Using a Korean Clinical Research Database
  • Inwhee Park
  • Seung Soo Sheen
  • Hong-Seok Lim
  • Dukyong Yoon
  • Man Young Park
  • Suk-Hyang Lee
  • Gyu-Tae Shin
  • Heungsoo Kim
  • Rae Woong Park
Original Research Article


Background and Aim

Clinical use of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) is associated with hyperkalemia as an adverse drug reaction. Although it has significant clinical implications, the incidence and relative risks of hyperkalemia with various ARBs have not yet been fully evaluated. The purpose of this study was to determine the risk of hyperkalemic events in hospitalized patients treated with different ARBs and to compare the risk among them.


We constructed a retrospective cohort composed of hospitalized adult patients who took ARBs in a single tertiary teaching hospital between April 2004 and March 2010. We estimated the incidence of hyperkalemia (serum potassium level >5.5 mEq/L) with various ARBs, and then compared the risk between them using a multivariate Cox proportional hazard model based on age, sex, Charlson co-morbidity score, baseline serum potassium, underlying diseases, and concomitant drugs.


We identified 6992 evaluable intervals from 5449 patients treated with one of the seven ARBs during hospitalization over the 71-month study period with 2521.6 patient-months. We found 381 hyperkalemic events (5.4%) during the study period and an overall event rate of 15.1/100 patient-months. Moderate to fatal hyperkalemia was relatively rare (>6.0 mEq/L, 2.1% [moderate]; >6.5 mEq/L, 0.9% [severe]; >7.0 mEq/L, 0.3% [fatal]). After adjustment for covariates, telmisartan showed a lower risk of hyperkalemia (hazard ratio 0.67; 95% confidence interval 0.51, 0.89) compared with all other ARBs.


The risk of hyperkalemic events in hospitalized patients treated with different ARBs was defined. Telmisartan showed a relatively lower hyperkalemic risk profile in hospitalized patients compared with other ARBs.


Telmisartan Olmesartan Nabumetone Serum Potassium Level Aceclofenac 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0026116, 2012-0000995, RWP, RWP). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

The authors declare no conflicts of interest.

Inwhee Park and Seung Soo Sheen contributed equally to this work.


  1. 1.
    Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002 Mar 23; 359 (9311): 995–1003PubMedCrossRefGoogle Scholar
  2. 2.
    Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001 Sep 20; 345 (12): 851–60PubMedCrossRefGoogle Scholar
  3. 3.
    Schrader J, Luders S, Kulschewski A, et al. Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES). Stroke 2005 Jun; 36 (6): 1218–26PubMedCrossRefGoogle Scholar
  4. 4.
    Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000 Feb 19; 355 (9204): 637–45PubMedCrossRefGoogle Scholar
  5. 5.
    Thompson CA. New angiotensin-receptor blocker approved by FDA. Am J Health Syst Pharm 2011 Apr 1; 68 (7): 550Google Scholar
  6. 6.
    Shier DN, Kusano E, Stoner GD, et al. Production of renin, angiotensin II, and aldosterone by adrenal explant cultures: response to potassium and converting enzyme inhibition. Endocrinology 1989 Jul; 125 (1): 486–91PubMedCrossRefGoogle Scholar
  7. 7.
    Granger CB, Ertl G, Kuch J, et al. Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors. Am Heart J 2000 Apr; 139 (4): 609–17PubMedCrossRefGoogle Scholar
  8. 8.
    Sadjadi SA, McMillan JI, Jaipaul N, et al. A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers. Ther Clin Risk Manag 2009 Jun; 5 (3): 547–52PubMedGoogle Scholar
  9. 9.
    Winkelmayer WC, Zhang Z, Shahinfar S, et al. Efficacy and safety of angiotensin II receptor blockade in elderly patients with diabetes. Diabetes Care 2006 Oct; 29 (10): 2210–7PubMedCrossRefGoogle Scholar
  10. 10.
    Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008 Apr 10; 358 (15): 1547–59PubMedCrossRefGoogle Scholar
  11. 11.
    Bootsma JE, Warle-van Herwaarden MF, Verbeek AL, et al. Adherence to biochemical monitoring recommendations in patients starting with Renin Angiotensin system inhibitors: a retrospective cohort study in the Netherlands. Drug Saf 2011 Jul 1; 34 (7): 605–14PubMedCrossRefGoogle Scholar
  12. 12.
    Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North Am 2005 Aug; 23 (3): 723–47, viii-ixPubMedCrossRefGoogle Scholar
  13. 13.
    Park MY, Yoon D, Lee K, et al. A novel algorithm for detection of adverse drug reaction signals using a hospital electronic medical record database. Pharmacoepidemiol Drug Saf 2011 Jun; 20 (6): 598–607PubMedCrossRefGoogle Scholar
  14. 14.
    Yoon D, Park M, Choi N, et al. Detection of Adverse drug reaction signals using an electronic health records database: Comparison of the Laboratory Extreme Abnormality Ratio (CLEAR). Clin Pharmacol Ther 2012 Mar; 91 (3): 467–74PubMedCrossRefGoogle Scholar
  15. 15.
    Shlipak MG. Pharmacotherapy for heart failure in patients with renal insufficiency. Ann Intern Med 2003 Jun 3; 138 (11): 917–24PubMedCrossRefGoogle Scholar
  16. 16.
    Sundararajan V, Henderson T, Perry C, et al. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004 Dec; 57 (12): 1288–94PubMedCrossRefGoogle Scholar
  17. 17.
    Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999 Mar 16; 130 (6): 461–70Google Scholar
  18. 18.
    Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001 Dec 6; 345 (23): 1667–75PubMedCrossRefGoogle Scholar
  19. 19.
    Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003 Nov 13; 349 (20): 1893–906PubMedCrossRefGoogle Scholar
  20. 20.
    Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med 2004 Aug 5; 351 (6): 585–92PubMedCrossRefGoogle Scholar
  21. 21.
    Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004 May 4; 109 (17): 2054–7PubMedCrossRefGoogle Scholar
  22. 22.
    Sanchez RA, Masnatta LD, Pesiney C, et al. Telmisartan improves insulin resistance in high renin nonmodulating salt-sensitive hypertensives. J Hypertens 2008 Dec; 26 (12): 2393–8PubMedCrossRefGoogle Scholar
  23. 23.
    Schmidt B, Schieffer B. Angiotensin II AT1 receptor antagonists. Clinical implications of active metabolites. J Med Chem 2003 Jun 5; 46 (12): 2261–70Google Scholar
  24. 24.
    Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med 2005 Sep–Oct; 20 (5): 272–90PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Inwhee Park
    • 1
  • Seung Soo Sheen
    • 2
  • Hong-Seok Lim
    • 3
  • Dukyong Yoon
    • 4
  • Man Young Park
    • 4
  • Suk-Hyang Lee
    • 5
  • Gyu-Tae Shin
    • 1
  • Heungsoo Kim
    • 1
  • Rae Woong Park
    • 4
  1. 1.Department of NephrologyAjou University School of MedicineSuwon, Gyeonggi-doRepublic of Korea
  2. 2.Department of Pulmonary and Critical Care MedicineAjou University School of MedicineSuwon, Gyeonggi-doRepublic of Korea
  3. 3.Department of CardiologyAjou University School of MedicineSuwon, Gyeonggi-doRepublic of Korea
  4. 4.Department of Biomedical InformaticsAjou University School of MedicineWonchon-dong, Yeongtong-gu, Suwon, Gyeonggi-doRepublic of Korea
  5. 5.College of PharmacyAjou UniversitySuwon, Gyeonggi-doRepublic of Korea

Personalised recommendations